title: Exploring glyoxalase 1 expression in prostate cancer tissues: targeting the enzyme by ethyl pyruvate defangs some malignancy-associated properties.
abstract: BACKGROUND
  The glyoxalase (GLO)1 is part of a ubiquitous detoxification system in the glycolytic pathway of normal and tumor cells. It protects against cellular damage caused by cytotoxic metabolites.
  
  
  METHODS
  Aiming at exploring the role of GLO1 in prostate cancer, we evaluated and targeted the expression of GLO1 in prostate cancer tissues and cell lines and analyzed its correlation with grading systems and tumor growth indices.
  
  
  RESULTS
  Immunohistochemical studies on 37 prostate cancer specimens revealed a positive correlation between Helpap-grading and the cytoplasmic (P = 0.002)/nuclear (P = 0.006) GLO1 level. A positive correlation between Ki-67 proliferation marker and the cytoplasmic GLO1 (P = 0.006) was evident. Furthermore, the highest GLO1 level was detected in the androgen-sensitive LNCaP compared to the androgen-independent Du-145 and PC-3 prostate cell lines and the breast cancer cell MCF-7, both at protein and mRNA level. Treating cancer cells with ethyl pyruvate was found to defang some malignancy-associated properties of cancer cells including proliferation, invasion and anchorage-independent growth. In vitro results revealed that the potency of ethyl pyruvate is increased when cells are metabolically activated by growth stimulators, for example, by fetal calf serum, dihydrotestosterone, tumor growth factor-β1 and leptin.
  
  
  CONCLUSIONS
  The positive correlation of GLO1 expression level in prostate cancer tissues with the pathological grade and proliferation rate may assign GLO1 as a risk factor for prostate cancer development and progression. Furthermore, our data indicate that inhibitors of GLO1 might be useful to decelerate the cancer cell growth by a novel therapeutic approach that we may call "induced metabolic catastrophe."
authors.affiliation: Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Baunacke
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Susanne
authors.initials: S
authors.lastname: Trettner
authors.forename: Kathrin M Y
authors.initials: KM
authors.lastname: Engel
authors.forename: Nasr Y A
authors.initials: NY
authors.lastname: Hemdan
authors.forename: Volker
authors.initials: V
authors.lastname: Wiechmann
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Stolzenburg
authors.forename: Marina
authors.initials: M
authors.lastname: Bigl
authors.forename: Gerd
authors.initials: G
authors.lastname: Birkenmeier
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D061986:MCF-7 Cells; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011773:Pyruvates / Q000008:administration & dosage*; D016037:Single-Blind Method
chemical_list: D014408:Biomarkers, Tumor; D011773:Pyruvates; C046522:ethyl pyruvate; D007791:Lactoylglutathione Lyase
keywords: ethyl pyruvate; glyoxalase 1; immunohistochemistry; prostate cancer